GB9305735D0 - Novel agent for controlling cell activity - Google Patents

Novel agent for controlling cell activity

Info

Publication number
GB9305735D0
GB9305735D0 GB939305735A GB9305735A GB9305735D0 GB 9305735 D0 GB9305735 D0 GB 9305735D0 GB 939305735 A GB939305735 A GB 939305735A GB 9305735 A GB9305735 A GB 9305735A GB 9305735 D0 GB9305735 D0 GB 9305735D0
Authority
GB
United Kingdom
Prior art keywords
domain
agent
cell
cell activity
endosome
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
GB939305735A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to GB939305735A priority Critical patent/GB9305735D0/en
Publication of GB9305735D0 publication Critical patent/GB9305735D0/en
Priority to ES94909262T priority patent/ES2183836T3/en
Priority to SG1996007056A priority patent/SG73411A1/en
Priority to SK1155-95A priority patent/SK115595A3/en
Priority to CA002158647A priority patent/CA2158647A1/en
Priority to PT94909262T priority patent/PT689459E/en
Priority to PL94310698A priority patent/PL178895B1/en
Priority to PCT/GB1994/000558 priority patent/WO1994021300A1/en
Priority to KR1019950703985A priority patent/KR960700756A/en
Priority to AT94909262T priority patent/ATE228856T1/en
Priority to HU9502673A priority patent/HU217220B/en
Priority to NZ262484A priority patent/NZ262484A/en
Priority to JP52080694A priority patent/JP4300265B2/en
Priority to DE69431832T priority patent/DE69431832T2/en
Priority to AU62175/94A priority patent/AU671203C/en
Priority to CZ952426A priority patent/CZ242695A3/en
Priority to BR9406232A priority patent/BR9406232A/en
Priority to EP94909262A priority patent/EP0689459B1/en
Priority to DK94909262T priority patent/DK0689459T3/en
Priority to CNB941921255A priority patent/CN1195551C/en
Priority to IL10904594A priority patent/IL109045A0/en
Priority to IN200MA1994 priority patent/IN178499B/en
Priority to NO953643A priority patent/NO953643L/en
Priority to FI954390A priority patent/FI954390A/en
Priority to US11/819,647 priority patent/US20080070278A1/en
Priority to JP2007211720A priority patent/JP4740206B2/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.
GB939305735A 1993-03-19 1993-03-19 Novel agent for controlling cell activity Pending GB9305735D0 (en)

Priority Applications (26)

Application Number Priority Date Filing Date Title
GB939305735A GB9305735D0 (en) 1993-03-19 1993-03-19 Novel agent for controlling cell activity
CNB941921255A CN1195551C (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity
JP52080694A JP4300265B2 (en) 1993-03-19 1994-03-18 Novel agents for controlling cellular activity
AU62175/94A AU671203C (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity
SK1155-95A SK115595A3 (en) 1993-03-19 1994-03-18 An agent for controlling cell interaction with its external environment and application this agent
CA002158647A CA2158647A1 (en) 1993-03-19 1994-03-18 Conjugate containing botulinum toxin translocation and effector domains and heterologocus binding domain for the targeted control of cell activity
PT94909262T PT689459E (en) 1993-03-19 1994-03-18 NEW AGENT FOR THE CONTROL OF CELLULAR ACTIVITY
PL94310698A PL178895B1 (en) 1993-03-19 1994-03-18 Novell cell activity controlling factor
PCT/GB1994/000558 WO1994021300A1 (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity
KR1019950703985A KR960700756A (en) 1993-03-19 1994-03-18 NOVEL AGENT FOR CONTROLLING GELL ACTIVITY
AT94909262T ATE228856T1 (en) 1993-03-19 1994-03-18 AGENT FOR CONTROLLING CELL ACTIVITY
HU9502673A HU217220B (en) 1993-03-19 1994-03-18 Process for producing of novel agent for controlling cell activity
NZ262484A NZ262484A (en) 1993-03-19 1994-03-18 An agent for controlling the interaction of a cell with its environment by controlling the transport of intergal membrane proteins (imp)
ES94909262T ES2183836T3 (en) 1993-03-19 1994-03-18 NEW AGENT TO CONTROL THE CELLULAR ACTIVITY.
DE69431832T DE69431832T2 (en) 1993-03-19 1994-03-18 MEANS FOR CONTROLLING CELL ACTIVITY
SG1996007056A SG73411A1 (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity
CZ952426A CZ242695A3 (en) 1993-03-19 1994-03-18 Agent for regulation of a cell interaction with its outer environment, process of its preparation, regulation method of the cell interaction with its outer environment and the use of such agent
BR9406232A BR9406232A (en) 1993-03-19 1994-03-18 New agent to control cell activity
EP94909262A EP0689459B1 (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity
DK94909262T DK0689459T3 (en) 1993-03-19 1994-03-18 Agent for controlling cell activity
IL10904594A IL109045A0 (en) 1993-03-19 1994-03-20 Agent for controlling cell activity and its manufacture
IN200MA1994 IN178499B (en) 1993-03-19 1994-03-21
NO953643A NO953643L (en) 1993-03-19 1995-09-15 New means of controlling cell activity
FI954390A FI954390A (en) 1993-03-19 1995-09-18 New agent control of cell activity
US11/819,647 US20080070278A1 (en) 1993-03-19 2007-06-28 Novel agent for controlling cell activity
JP2007211720A JP4740206B2 (en) 1993-03-19 2007-08-15 Novel agents for controlling cellular activity

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB939305735A GB9305735D0 (en) 1993-03-19 1993-03-19 Novel agent for controlling cell activity

Publications (1)

Publication Number Publication Date
GB9305735D0 true GB9305735D0 (en) 1993-05-05

Family

ID=10732382

Family Applications (1)

Application Number Title Priority Date Filing Date
GB939305735A Pending GB9305735D0 (en) 1993-03-19 1993-03-19 Novel agent for controlling cell activity

Country Status (24)

Country Link
US (1) US20080070278A1 (en)
EP (1) EP0689459B1 (en)
JP (2) JP4300265B2 (en)
KR (1) KR960700756A (en)
CN (1) CN1195551C (en)
AT (1) ATE228856T1 (en)
AU (1) AU671203C (en)
BR (1) BR9406232A (en)
CA (1) CA2158647A1 (en)
CZ (1) CZ242695A3 (en)
DE (1) DE69431832T2 (en)
DK (1) DK0689459T3 (en)
ES (1) ES2183836T3 (en)
FI (1) FI954390A (en)
GB (1) GB9305735D0 (en)
HU (1) HU217220B (en)
IL (1) IL109045A0 (en)
IN (1) IN178499B (en)
NO (1) NO953643L (en)
NZ (1) NZ262484A (en)
PL (1) PL178895B1 (en)
PT (1) PT689459E (en)
SG (1) SG73411A1 (en)
SK (1) SK115595A3 (en)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9305735D0 (en) * 1993-03-19 1993-05-05 North John R Novel agent for controlling cell activity
GB9617671D0 (en) 1996-08-23 1996-10-02 Microbiological Res Authority Recombinant toxin fragments
US7192596B2 (en) * 1996-08-23 2007-03-20 The Health Protection Agency Ipsen Limited Recombinant toxin fragments
ATE227739T1 (en) * 1998-05-13 2002-11-15 Biotecon Ges Fuer Biotechnologische Entwicklung & Consulting Mbh HYBRID PROTEIN FOR INHIBITING MAST CELL DEGRANULATION AND ITS USE
GB9922554D0 (en) * 1999-09-23 1999-11-24 Microbiological Res Authority Inhibition of secretion from non-neuronal cells
GB9926875D0 (en) * 1999-11-12 2000-01-12 Microbiological Research Agenc Use of lytic toxins and toxin conjugates
GB0321344D0 (en) * 2003-09-11 2003-10-15 Health Prot Agency Re-targeted toxin conjugates
DE602004025781D1 (en) * 2003-11-14 2010-04-15 Starhome Gmbh Control of incoming calls for roaming subscribers of a cellular mobile network
US8399400B2 (en) * 2004-12-01 2013-03-19 Syntaxin, Ltd. Fusion proteins
US7659092B2 (en) * 2004-12-01 2010-02-09 Syntaxin, Ltd. Fusion proteins
US8512984B2 (en) 2004-12-01 2013-08-20 Syntaxin, Ltd. Non-cytotoxic protein conjugates
US8778634B2 (en) 2004-12-01 2014-07-15 Syntaxin, Ltd. Non-cytotoxic protein conjugates
US8603779B2 (en) 2004-12-01 2013-12-10 Syntaxin, Ltd. Non-cytotoxic protein conjugates
GB0426394D0 (en) * 2004-12-01 2005-01-05 Health Prot Agency Fusion proteins
US8796216B2 (en) 2008-06-12 2014-08-05 Syntaxin Limited Suppression of neuroendocrine diseases
EP2310028B1 (en) * 2008-06-12 2016-11-16 Ipsen Bioinnovation Limited Fusion proteins for use in the treatment of acromegaly
US9623117B2 (en) * 2011-04-04 2017-04-18 Wisconsin Alumni Research Foundation Method for selective targeting and entry of bacterial toxins to cells
GB201312317D0 (en) 2013-07-09 2013-08-21 Syntaxin Ltd Cationic neurotoxins
US10647750B2 (en) 2015-01-09 2020-05-12 Ipsen Bioinnovation Limited Cationic neurotoxins
GB201517450D0 (en) 2015-10-02 2015-11-18 Ipsen Biopharm Ltd Method
EP3263710A1 (en) 2016-07-01 2018-01-03 Ipsen Biopharm Limited Production of activated clostridial neurotoxins
JP7186228B2 (en) 2018-02-26 2022-12-08 イプセン バイオファーム リミテッド Use of ultrasound to guide injection of non-cytotoxic proteases
GB201815817D0 (en) 2018-09-28 2018-11-14 Ispen Biopharm Ltd Clostridial neurotoxins comprising and exogenous activation loop
GB201900621D0 (en) 2019-01-16 2019-03-06 Ipsen Biopharm Ltd Labelled polypeptides
GB201914034D0 (en) 2019-09-30 2019-11-13 Ipsen Biopharm Ltd Treatment of neurological disorders
GB202100566D0 (en) 2021-01-15 2021-03-03 Ipsen Biopharm Ltd Treatment of brain damage
GB202104294D0 (en) 2021-03-26 2021-05-12 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an exogenous activation loop
EP4297773A1 (en) 2021-03-30 2024-01-03 Ipsen Biopharm Limited Catalytically inactive clostridial neurotoxins for the treatment of pain & inflammatory disorders
JP2024513191A (en) 2021-03-30 2024-03-22 イプセン バイオファーム リミテッド Treatment of pain and inflammatory disorders
GB202116795D0 (en) 2021-11-22 2022-01-05 Ipsen Biopharm Ltd Treatment of visceral pain
GB202214229D0 (en) 2022-09-28 2022-11-09 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an activating endosomal protease cleavage site
GB202214232D0 (en) 2022-09-28 2022-11-09 Ispen Biopharm Ltd Clostridial neurotoxins comprising an activating exogenous protease cleavage site

Family Cites Families (8)

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US4664911A (en) * 1983-06-21 1987-05-12 Board Of Regents, University Of Texas System Immunotoxin conjugates employing toxin B chain moieties
US5668255A (en) * 1984-06-07 1997-09-16 Seragen, Inc. Hybrid molecules having translocation region and cell-binding region
EP0329184A3 (en) * 1988-02-19 1990-05-23 Neorx Corporation Antimers and antimeric conjugation
US5045451A (en) * 1988-10-26 1991-09-03 Board Of Regents Methods for screening antibodies for use as immunotoxins
WO1990010692A1 (en) * 1989-03-15 1990-09-20 University Of Florida Monoclonal antibody for use in detection and treatment of childhood leukemia
US5300496A (en) * 1991-09-30 1994-04-05 The University Of British Columbia Complexed vanadium for the treatment of diabetes mellitus
US5877295A (en) * 1992-09-30 1999-03-02 The Center For Blood Research Antibodies which bind a subpopulation of Mac-1 (CD11b/CD18) molecules which mediate neutrophil adhesion to ICAM-1 and fibrinogen
GB9305735D0 (en) * 1993-03-19 1993-05-05 North John R Novel agent for controlling cell activity

Also Published As

Publication number Publication date
EP0689459A1 (en) 1996-01-03
WO1994021300A2 (en) 1994-09-29
SK115595A3 (en) 1997-02-05
JPH09500867A (en) 1997-01-28
FI954390A (en) 1995-11-17
HU9502673D0 (en) 1995-11-28
AU6217594A (en) 1994-10-11
HUT76556A (en) 1997-09-29
NO953643L (en) 1995-11-16
US20080070278A1 (en) 2008-03-20
DK0689459T3 (en) 2003-03-24
ES2183836T3 (en) 2003-04-01
DE69431832D1 (en) 2003-01-16
BR9406232A (en) 1996-01-09
CZ242695A3 (en) 1996-04-17
AU671203B2 (en) 1996-08-15
CN1195551C (en) 2005-04-06
JP4740206B2 (en) 2011-08-03
PL178895B1 (en) 2000-06-30
FI954390A0 (en) 1995-09-18
EP0689459B1 (en) 2002-12-04
DE69431832T2 (en) 2003-04-10
JP2007302696A (en) 2007-11-22
SG73411A1 (en) 2000-06-20
CA2158647A1 (en) 1994-09-29
KR960700756A (en) 1996-02-24
IN178499B (en) 1997-05-03
ATE228856T1 (en) 2002-12-15
NO953643D0 (en) 1995-09-15
IL109045A0 (en) 1994-06-24
JP4300265B2 (en) 2009-07-22
PL310698A1 (en) 1995-12-27
AU671203C (en) 2003-02-27
NZ262484A (en) 1996-08-27
PT689459E (en) 2003-04-30
HU217220B (en) 1999-12-28
CN1124929A (en) 1996-06-19

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